Sawyers said the new drugs bind tightly enough to the natural hormone-binding site on androgen receptors to prevent most of them from functioning even in cells with a lot of androgen receptors. Bicalutamide interferes with the receptor through a different mechanism, which backfires, when too much androgen receptor is present, Sawyers explained.
The promising laboratory studies led Medivation to license the drugs for commercial development, said Sawyers, who serves as a consultant to the company and would receive royalties on the drug should it prove to be successful.
The company chose to use MDV3100 for clinical studies, which began in 2007. In those initial studies, 30 men with antiandrogen-resistant prostate cancer received low doses of MDV3100. Twenty-two of those men showed a sustained decline in their blood levels of prostate specific antigen (PSA), an indication that their cancer was responding favorably to the drug. This trial is still under way, and results from a total of 140 patients receiving higher doses of the drug will be reported within the next year, said Sawyers.
Medivation has received permission from the Food and Drug Administration for a large clinical trial of MDV3100 on about 1,200 patients with antiandrogen-resistant disease. This study will assess MDV3100's effect on cancer survival and will take several years.
While these preliminary results are promising, Sawyers said his laboratory will continue to seek further improvements in drug therapy for prostate cancer. "There were some men in the initial trial in which the drug didn't work at all, and we want to find out why," he said. "It may be because the drug is not potent enough to overcome resistance due to androgen receptor overexpression. Or, it may b
|Contact: Jennifer Michalowski|
Howard Hughes Medical Institute